The bacteriophage functional genomics and bioinformatics study described in this proposal is interdisciplinary and undergraduate student-driven. It addresses the three major AREA program objectives by supporting meritorious research, exposing undergraduates to biomedical research, and strengthening the research environment at a non-research intensive school. The proposal specifically addresses the NIAID's objective to acquire knowledge that will eventually lead to the treatment and prevention of an infectious disease, Buruli ulcer. Buruli ulcer is an important, neglected disease of many third world nations in Central America, Africa, and Southeast Asia. Mycobacterium ulcerans, the causative agent of Buruli ulcer, is susceptible to infection and lysis by bacteriophages. Because bacteriophages have evolved strategies to manipulate the molecular machinery of their hosts, they are valuable tools in bacteriology. By isolating environmental mycobacteriophages, then sequencing and studying the genomes of eight of these phages, we will explore the biology of both phage and host. In the process, we anticipate the discovery of phage proteins that regulate bacterial growth, promote cell death, or genetically modify the host. This information is likely to contribute to the development of new tools for diagnosis, treatment, and prevention of this important bacterial disease. Our preliminary efforts toward this project show that we have the capability to isolate novel phages from the environment, sequence and annotate their genomes, and analyze the predicted protein-coding genes. We further have demonstrated the expertise to design and develop bioinformatics software to answer specific, relevant questions in phage genomics. Collectively, this work has involved 10 undergraduate students, with two more joining the research group in the summer of 2009. This study will provide students with an opportunity for learning how to ask and answer questions that can have a real impact on public health in some of the world's poorest places. The students understand and appreciate these potential humanitarian benefits, and these in turn motivate them toward continued involvement in biomedical research beyond their undergraduate years. The interdisciplinary approach exposes students to comparative, computational methods in addition to standard molecular techniques, and should build an appreciation for computational biology within our department and university. PUBLIC HEALTH RELEVANCE: This study proposes to learn about the bacteriophages that infect Mycobacterium ulcerans, a human pathogen that causes the neglected disease known as Buruli ulcer. There is potential to identify bacteriophage proteins that could be used for genetic manipulation of the host, including for vaccine development. In addition, phage proteins identified that are toxic to the bacterium might be useful in developing a therapy for the disease.